GEN News Highlights

Gene Tied to Emergence of Chemotherapy Resistance

(Page
1
of
1)

Researchers say analyzing a particular gene in high-grade serous cancer (HGSC) could help predict whether a patient’s tumor is likely to become resistant to chemotherapy over time. A team headed by researchers at the Peter MacCallum Cancer Center in Melbourne, Australia, has found that the emergence of treatment resistance in HGSC is associated with a loss or downregulation of the lipid transporter LRPB1 in the tumor.

Peter Bowtell, Ph.D., and colleagues used SNP arrays to examine both spatial and temporal genomic variation in metastatic lesions from individual patients and 22 paired pretreatment and post-treatment tumor samples to evaluate spatial and temporal genomic variation. Spatial variation refers to the level of differential gene expression within tumor cells in the same patient at a single time point. Temporal variation provides an indication of how much genetic change occurs in the tumor over time.

What they found was that tumors that were initially sensitive to chemotherapy but subsequently became resistant had developed more genetic changes than those that were resistant to chemotherapy from the start. Notably, deletion or downregulation of the lipid transporter LRP1B emerged as a significant correlate. And when the team then either deleted or forced overexpression of the LRP1B gene in cell lines, they found that reducing LRP1B expression reduced cancer cell sensitivity to liposomal doxorubicin (but not doxorubicin), LRP1B overexpression was enough to increase the cancer cells’ sensitivity to doxorubicin.

“We were surprised by the extent of variation that was present among the tumor deposits collected at surgery, and by how far the tumors could evolve during therapy,” Dr. Bowtell remarks. “The existence of multiple cancer genomes in an individual patient could provide many opportunities for the cancer to circumvent chemotherapy and may help explain why it has been so difficult to make progress with the disease.”

The researchers point out that it's currently not easy to predict which women with ovarian cancer will become resistant to chemotherapy over time. “LRP1B adds to a handful of other mechanisms so far identified,” Dr. Bowtell states. “If we can comprehensively map the mechanisms that confer resistance, we may be able to predict whether some women are likely to respond to a certain drug or not, and find ways of reversing resistance.

Jobs

GEN Jobs powered by HireLifeScience.com connects you directly to employers in pharma, biotech, and the life sciences. View 40 to 50 fresh job postings daily or search for employment opportunities including those in R&D, clinical research, QA/QC, biomanufacturing, and regulatory affairs.

Be sure to take the GEN Poll

Climate Change

How would you describe the researchers response to the 2°C global temperature target?

They are right on the mark. A 2°C global temperature rise will push us further over the edge. We have to set a lower target.

A 2°C global temperature rise is a reasonable target on which to focus in order to diminish the impact of climate change.

We have already gone beyond the threshold for getting a handle on climate change. So now we just need to learn how to adapt to the inexorable climatic changes with which we will have to deal going forward.

They are right on the mark. A 2°C global temperature rise will push us further over the edge. We have to set a lower target.

40.0%

A 2°C global temperature rise is a reasonable target on which to focus in order to diminish the impact of climate change.

20.0%

We have already gone beyond the threshold for getting a handle on climate change. So now we just need to learn how to adapt to the inexorable climatic changes with which we will have to deal going forward.

If you have any questions about your subscription, click
hereto email us or call at (914) 740-2189.

You may also be interested in subscribing to the GEN magazine, an indispensable
resource for everyone involved in the business of translating discoveries at the
bench into solutions that fight disease and improve health, agriculture, and the
environment. Subscribe
today to see why over 60,000 biotech professionals read GEN to
keep current in the areas of genomics, proteomics, drug discovery, biomarker discovery,
bioprocessing, molecular diagnostics, collaborations, biotech business trends, and
more.